Caprine arthritis encephalitis virus (CAEV) belongs to the lentivirus subfamily of retroviruses. It integrates into the host cell genome and induces a persistent infection of domestic goats. CAEV infection causes encephalomyelitis in young goats, and mastitis, chronic progressive arthritis and synovitis in adult goats. The arthritis which results is similar in pathology to rheumatoid arthritis (RA) in humans. There is recent evidence that a novel CAEV variant occurs in humans and generates immune cross-reactivity to human immunodeficiency virus- I (IUV- 1). It is evident that CAEV is important not only as a pathogen in goats but as a vehicle for studying human diseases. We will use CAEV-induced disease 'in goats as a model to study the pathogenetic mechanisms of lentiviruses and also to investigate further some of the mechanisms that lead to arthritis. The obiective of this proposed project is to study molecular mechanisms of CAEV pathogenesis. This is important in the light of the possible use of CAEV-1ike lentivuiuses as -prophylactic agents against human viruses like EDIV-1. Specifically we propose to: i) investigate virus-host cell interactions by identifying and characterizing cell surface receptor(s) and defining the role of viral gp 13 5 and i do tha are essential for interaction with the cellular receptors; and ii) investigate some mechanisms that may be involved in the initiation and progression of arthritis by determining the role of various cytokines and chemokines, oxygen radicals, intracellular calcium fluctuations, circulating immune complexes, rheumatoid factor and also by identifying genes that are differentially transcribed during the infection. These results will provide a better understanding of a disease condition that is very similar to RA and in which the etiology is known.